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Multiple courses versus a single course of antenatal corticosteroids (ACS) have been associated with mild respiratory benefits but also adverse outcomes like smaller head circumference and birth weight. Long-term effects warrant study. We systematically reviewed long-term outcomes (≥1 year) in both preterm and term birth after exposure to preterm multiple courses (including a rescue dose or course) versus a single course. We searched seven databases from January 2000 to October 2021. We included follow-up studies of randomized controlled trials (RCTs) and cohort studies with births occurring in/after the year 2000, given advances in perinatal care. Two reviewers assessed titles/abstracts, articles, quality, and outcomes including psychological disorders, neurodevelopment, and anthropometry. Six follow-up studies of three RCTs and two cohort studies (over 2,860 children total) met inclusion criteria. Among children born preterm, randomization to multiple courses versus a single course of ACS was not associated with adjusted beneficial or adverse neurodevelopmental/psychological or other outcomes, but data are scant after a rescue dose (120 and 139 children, respectively, low certainty) and nonexistent after a rescue course. For children born at term (i.e., 27% of the multiple courses of ACS 5-year follow-up study of 1,728 preterm/term born children), preterm randomization to multiple courses (at least one additional course) versus a single course was significantly associated with elevated odds of neurosensory impairment (adjusted odds ratio = 3.70, 95% confidence interval: 1.57–8.75; 212 and 247 children, respectively, moderate certainty). In this systematic review of long-term outcomes after multiple courses versus a single course of ACS, there were no significant benefits or risks regarding neurodevelopment in children born preterm but little data after one rescue dose and none after a rescue course. However, multiple courses (i.e., at least one additional course) should be considered cautiously: after term birth, there are no long-term benefits but neurosensory harms. Key Points We systematically reviewed the long-term impact of multiple versus a single course of ACS. Long-term follow-up data were scant after a rescue dose and absent after one rescue course of ACS. In children born preterm, multiple courses of ACS were not associated with long-term benefits/harms. In children born at term, multiple courses of ACS were associated with neurosensory impairment. Preterm administration of multiple courses of ACS should be considered cautiously. [ABSTRACT FROM AUTHOR]

Objective In 2014, the leading obstetric societies published an executive summary of a joint workshop to establish obstetric interventions to be considered for periviable births. Antenatal corticosteroid administration between 22 0/7 and 22 6/7 weeks was not recommended given existing evidence. We sought to evaluate whether antenatal steroid exposure was associated with improved survival among resuscitated newborns delivered between 22 and 23 weeks of gestation. Study Design We conducted a population-based cohort study of all resuscitated livebirths delivered between 22 0/7 and 23 6/7 weeks of gestation in the United States during 2009 to 2014 utilizing National Center for Health Statistics data. The primary outcome was rate of survival to 1 year of life (YOL) between infant cohorts based on antenatal steroid exposure. Multivariable logistic regression estimated the association of antenatal steroid exposure on survival outcomes. Results In the United States between 2009 and 2014, there were 2,635 and 7,992 infants who received postnatal resuscitation after delivery between 22 0/7 to 22 6/7 and 23 0/7 to 23 6/7 weeks of gestation, respectively. Few infants born at 22 (15.9%) and 23 (26.0%) weeks of gestation received antenatal corticosteroids (ANCS). Among resuscitated neonates, survival to 1 YOL was 45.2 versus 27.8% (adjusted relative risk [aRR]: 1.6, 95% confidence interval [CI]: 1.2–2.1) and 57.9 versus 47.7% (aRR: 1.3, 95% CI: 1.1–1.5) for infants exposed to ANCS compared with those not exposed at 22 and 23 weeks of gestation, respectively. When stratified by 100 g birth weight category, ANCS were associated with survival among neonates weighing 500 to 599 g (aRR: 1.9, 95% CI: 1.3–2.9) and 600 to 699 g (aRR: 1.7, 95% CI: 1.1–2.6) at 22 weeks. Conclusion Exposure to ANCS was associated with higher survival rates to 1 YOL among resuscitated infants born at 22 and 23 weeks. National guidelines recommending against ANCS utilization at 22 weeks should be re-evaluated given emerging evidence of benefit. Key Points Exposure to antenatal steroids was associated with higher survival rates at 22 and 23 weeks of gestation. Women exposed to antenatal steroids were more likely to have an adverse outcome. The association between steroids and survival was observed among infants with birth weights > 500 g. [ABSTRACT FROM AUTHOR]

Objective Umbilical artery Doppler (UAD) velocimetry abnormalities are associated with increased neonatal morbidity and mortality. Currently, there are no risk stratification methods to assist in antepartum management such as timing of antenatal corticosteroids (ACS). Therefore, we sought to develop a model to predict risk of delivery within 7 days following diagnosis of abnormal UAD velocimetry in patients with fetal growth restriction (FGR). Study Design Retrospective single referral center study of liveborn singleton pregnancies complicated by FGR and ≥1 abnormal UAD velocimetry value (≥95th percentile for gestational age [GA]). We considered 17 variables and used backward stepwise logistic regression to create a multivariable model for the prediction of delivery within 7 days. We assessed model fit with calibration, discrimination, likelihood ratios, and area under the curve. Internal validation of the model was assessed by using the bootstrap method. Results Between 2008 and 2015, a total of 176 patients were eligible and included for model development. Median (range) GA at initial eligibility was 32.1 weeks (28.1–36.1 weeks) and from initial eligibility until delivery was 21 days (0–104 days). Fifty-two patients (30%) were delivered in the 7 days following inclusion. GA at first abnormal UAD, severity of first abnormal UAD, oligohydramnios, preeclampsia, and pre-pregnancy BMI were included in the model. The model had an area under the ROC curve of 0.94 (95% confidence interval [CI]: 0.90–0.98), sensitivity of 85%, and specificity of 91%. If the model alone were used for ACS timing, 85% of the cohort who delivered in the following week would have received ACS, and ACS would not have been given to 91% who delivered later. Internal validation yielded similar results with a mean area under the curve (95% CI) of 0.94 (0.88–0.98). Conclusion If validated externally, our model can be used to predict risk of delivery in patients with FGR and abnormal UAD velocimetry, potentially improving timing of ACS. Key Points Risk of delivery in seven days can be predicted. Risk of delivery can inform corticosteroid timing. External validation can further develop a clinical aid. [ABSTRACT FROM AUTHOR]

Objective In the antenatal late preterm steroids (ALPS) trial betamethasone significantly decreased short-term neonatal respiratory morbidity but increased the risk of neonatal hypoglycemia, diagnosed only categorically (<40 mg/dL). We sought to better characterize the nature, duration, and treatment for hypoglycemia. Study Design Secondary analysis of infants from ALPS, a multicenter trial randomizing women at risk for late preterm delivery to betamethasone or placebo. This study was a reabstraction of all available charts from the parent trial, all of which were requested. Unreviewed charts included those lost to follow-up or from sites not participating in the reabstraction. Duration of hypoglycemia (<40 mg/dL), lowest value and treatment, if any, were assessed by group. Measures of association and regression models were used where appropriate. Results Of 2,831 randomized, 2,609 (92.2%) were included. There were 387 (29.3%) and 223 (17.3%) with hypoglycemia in the betamethasone and placebo groups, respectively (relative risk [RR]: 1.69, 95% confidence interval [CI]: 1.46–1.96). Hypoglycemia generally occurred in the first 24 hours in both groups: 374/385 (97.1%) in the betamethasone group and 214/222 (96.4%) in the placebo group (p = 0.63). Of 387 neonates with hypoglycemia in the betamethasone group, 132 (34.1%) received treatment, while 73/223 (32.7%) received treatment in placebo group (p = 0.73). The lowest recorded blood sugar was similar between groups. Most hypoglycemia resolved by 24 hours in both (93.0 vs. 89.3% in the betamethasone and placebo groups, respectively, p = 0.18). Among infants with hypoglycemia in the first 24 hours, the time to resolution was shorter in the betamethasone group (2.80 [interquartile range: 2.03–7.03) vs. 3.74 (interquartile range: 2.15–15.08) hours; p = 0.002]. Persistence for >72 hours was rare and similar in both groups, nine (2.4%, betamethasone) and four (1.9%, placebo, p = 0.18). Conclusion In this cohort, hypoglycemia was transient and most received no treatment, with a quicker resolution in the betamethasone group. Prolonged hypoglycemia was uncommon irrespective of steroid exposure. Key Points Hypoglycemia was transient and approximately two-thirds received no treatment. Neonates in the ALPS trial who received betamethasone had a shorter time to resolution than those with hypoglycemia in the placebo group. Prolonged hypoglycemia occurred in approximately 2 out of 100 late preterm newborns, irrespective of antenatal steroid exposure. [ABSTRACT FROM AUTHOR]

Objective  A single course of synthetic antenatal corticosteroids is standard care for women considered to be at risk for preterm birth before 34 weeks of gestation. While the intended target is the fetal lung, the fetal brain contains remarkably high levels of glucocorticoid receptors in structures critical in the regulation of behavior and endocrine function. Negative programming signals may occur which can lead to permanent maladaptive changes and predispose the infant/child to an increased risk in physical, mental, and developmental disorders. Methods  Framed around these areas of concerns for physical, mental, and developmental disorders, this narrative review drew on studies (animal and clinical), evaluating the long-term effects of antenatal corticosteroids to present the case that a more targeted approach to the use of antenatal corticosteroids for the betterment of the fetus urgently needed. Results  Studies raised concerns about the potential negative long-term consequences, especially for the exposed fetus who was born beyond the period of the greatest benefit from antenatal corticosteroids. The long-term consequences are more subtle in nature and usually manifest later in life, often beyond the scope of most clinical trials. Conclusion  Continued research is needed to identify sufficient safety data, both short term and long term. Caution in the use of antenatal corticosteroids should be exercised while additional work is undertaken to optimize dosing strategies and better identify women at risk of preterm birth prior to administration of antenatal corticosteroids. Key Points A single-course ACS is a remarkable therapy with substantial benefits. There is a potential of long-term neurodevelopmental consequences in the ACS-exposed fetus. There is a need to improve dosing strategies and identification of appropriate at risk women. [ABSTRACT FROM AUTHOR]

Objective  The objective of this study was to evaluate the association between the method of maternal glycemic control after antenatal corticosteroid, administration and maternal hyperglycemia and neonatal morbidity among women with diabetes. Study Design  This was a retrospective cohort study of women with pregestational diabetes who received antenatal corticosteroids and delivered in <34 weeks. The primary maternal outcome was adequate glycemic control, defined as <50% of glucose values above goal (fasting <100 mg/dL, 2-hour postprandial <120 mg/dL, or <115 mg/dL on insulin infusion). The primary neonatal outcome was composite morbidity (continuous positive airway pressure, mechanical ventilation, intraventricular hemorrhage, or death). Demographic characteristics and outcomes were compared by the method of glycemic control and neonatal morbidity using chi-square test, Fisher's exact test, Mann–Whitney U -test, and Student's t -test, as appropriate. Results  Of 52 eligible women, only 1 (1.9%) had adequate maternal glycemic control. There was no significant association between the method of glycemic control and maternal hyperglycemia or neonatal morbidity. There was no association between maternal glucose and neonatal morbidity; however, neonates with composite morbidity were more likely to be born to women who received less insulin. Conclusion  Maternal glycemic control among women with diabetes was poor after the antenatal corticosteroid administration, regardless of glycemic control method. Neither the method of maternal glycemic control nor the degree of control was associated with neonatal morbidity. [ABSTRACT FROM AUTHOR]

Objective  The objective of this study was to measure knowledge and practice variation in late preterm steroid use. Study Design  Electronic survey of American College of Obstetricians and Gynecologists (ACOG) members about data supporting the ACOG/Society for Maternal-Fetal Medicine (SMFM) recommendations and practice when caring for women with anticipated late preterm birth (PTB), 34 0/7 to 36 6/7 weeks. Results  Of 352 administered surveys, we obtained 193 completed responses (55%); 82.5% were generalist obstetrician-gynecologists (OB/GYNs), and 42% cared for women with anticipated late PTB at least weekly. Most believed that late preterm steroids provided benefit by reducing respiratory distress syndrome (93%), transient tachypnea of the newborn (83%), and neonatal intensive care unit admission (82%). More than half administered late preterm steroids to women with multiple gestations (73%), and pregestational diabetes (55–80%) depending on glycemic control. OB/GYNs administered steroids to insulin-dependent and poorly controlled diabetics more often than MFMs (75 vs. 46% and 59 vs. 37% respectively, p  < 0.05 for both). While providers believed there was increased maternal hyperglycemia (88%) and neonatal hypoglycemia (59%), 88% believed neonatal respiratory benefits outweighed these risks. Respondents agreed research is needed to determine who are appropriate candidates (77%) and how to minimize adverse outcomes (82%). Conclusion  Most providers are administering late preterm steroids to all women, even those populations who have been excluded from previous trials. Despite widespread use, providers believe more research is needed to optimize management. [ABSTRACT FROM AUTHOR]

Since 1972, the beneficial neonatal effects of antenatal corticosteroids (ACSs) have been repeatedly demonstrated in pregnancies at risk of preterm birth before 34 weeks' gestation. While ACS utilization before 34 weeks has been high since the 1990s, knowledge gaps regarding the risks and benefits of ACS continue to exist. Recent evidence has been published regarding the benefit of ACS in the late preterm period. This review addresses the evidence and knowledge gaps for ACS use before and after 34 weeks' gestation. We also provide recommendations for ACS use in the late preterm period. [ABSTRACT FROM AUTHOR]

Objective A short cervix is an important risk factor for spontaneous preterm birth. There is substantial evidence that antenatal exposure to corticosteroids significantly benefits infants that are born when delivery occurs between 24 and 34 weeks' gestation and after 48 hours but within 7 days of their administration. Our study was to evaluate whether asymptomatic women who are given a course of antenatal corticosteroids (ACS) at the time a short cervix is identified deliver within the window of proven steroid benefit. Study Design This was a retrospective chart review of patients who had a cervical length of < 2.5 cmbetween 23 and 34 weeks and who did not have cervical dilation or significant symptoms of preterm labor. Results Of 367 asymptomatic patients with a short cervix, only two (0.5%) delivered within 7 days of the time a short cervix was identified.With a policy of giving ACS at the time an ultrasound shows a short cervix, 184 patients would have to be treated for each one who realizes a steroid benefit by delivering within 7 days. Conclusion We conclude that unless future studies show that neonates benefit from ACS givenmore than 7 days before delivery, giving ACS to asymptomatic women solely because the cervix is short is not advised. [ABSTRACT FROM AUTHOR]

Objective The aim of this study is to evaluate the impact of multiple pregnancies, maternal obesity, and preeclampsia on the effect of antenatal steroids on neonatal respiratory distress syndrome (RDS). Study Design The retrospective cohort study was performed in a level III maternity ward. Population was composed of mother-infant pairs. We included inborn infants < 34 weeks gestation, hospitalized in our neonatal intensive care unit, and mothers delivering before 34 weeks gestation and hospitalized before delivery. Primary measurement outcome was RDS. Results A total of 1,173 subjects were included: 535 mothers and 638 preterminfants. Antenatal corticosteroid (ACS) doses and pulmonary surfactant doses were negatively correlated (r = -0.15, p = 0.0002). Multiple logistic regression: lower gestational age and cesarean section were significantly associated with RDS in single pregnancies (odds ratio [OR], 95% confidence interval [CI]): 2.0 (1.7-2.4) and 3.6 (1.8-7.1), respectively; only gestational age was associated with RDS in twin or higher-order pregnancies: 2.7 (1.9-4.1) and 1.8 (0.6-5.4), respectively. Preterm infants of obese women did not receivemore pulmonary surfactant than other preterminfants: OR = 0.67 (0.13-1.40), neither did those born to women with hypertension or preeclampsia. Conclusion More ACS doses were associated with less pulmonary surfactant doses. Cesarean section and low gestational age increased the risk of RDS, independently from ACS administration, but maternal obesity and multiple pregnancies did not. [ABSTRACT FROM AUTHOR]

Objective This narrative review of the literature explores the current evidence and recommendations in favor of antenatal corticosteroids use during impending preterm deliveries as well as related issues and concerns. Study Design Synthesis of findings from published medical literature on antenatal corticosteroids and prematurity, retrieved from searches of computerized databases and authoritative texts. Results It is now recognized that an intramuscular course of betamethasone or dexamethasone given to a woman expected to deliver preterm not only accelerates pulmonary epithelial development but also matures other organ systems, significantly decreasing the chances of neonatal morbidities and increasing chances of survival. Conclusion There remain uncertainties over the efficacy of the established protocol in populations such as the very early preterm, the late preterm, and multiple gestations. Alternative regimens remain controversial because of fear of adverse effects and doubts regarding whether benefits outweigh risks. [ABSTRACT FROM AUTHOR]

We sought to quantify how often women with late preterm birth (LPTB) receive antenatal corticosteroid (ACS) therapy prior to 34 weeks and to determine its effects on neonatal respiratory morbidity. LPTBs (34 0/7 to 36 6/7 weeks) over a 1-year period at a single tertiary care hospital were studied. A composite neonatal respiratory outcome was defined as mechanical ventilation, continuous positive airway pressure with fraction of inspired oxygen (FIO2) >40% for >2 hours or FIO2 >40% for >4 hours within the first 72 hours of life. Multivariate logistic regression analysis was used to evaluate the association between ACS therapy and neonatal respiratory morbidity. Over the study period, 503 LPTBs met the study criteria and 6.8% (n=34) had ACS therapy <34 weeks. Most had exposure >7 days prior to delivery (64.7%). Almost one-half of those receiving prior ACS therapy delivered between 34 and 35 weeks. There was no difference in the rate of prior ACS therapy based on LPTB indication for delivery. After adjusting for confounding factors, prior ACS therapy was not associated with lower respiratory morbidity (odds ratio [OR] 2.0, 95% confidence interval [CI] 0.2 to 16.3, p=0.53). Advancing gestational age was the only variable associated with respiratory morbidity (OR 0.50, 95% CI 0.26 to .94, p=0.03). In our population, prior ACS therapy was infrequent and was not associated with improvements in neonatal respiratory morbidity following LPTB. [ABSTRACT FROM AUTHOR]

The optimal time interval between administration of antenatal corticosteroids and delivery is 1 to 7 days. This study evaluates the timing of the first course of antenatal corticosteroids in clinical practice. We performed a retrospective cohort study of consecutive women who had received antenatal corticosteroids and/or delivered between 24 and 34 weeks of gestation. Time between administration of corticosteroids and delivery was compared between women with different causes of anticipated preterm deliveries: symptomatic preterm labor with intact membranes; preterm premature rupture of the membranes; (pre)eclampsia; hemolysis, elevated liver enzymes, and low platelet count; intrauterine growth restriction; vaginal blood loss; and suspected fetal distress. We included 439 women of whom 348 (79%) completed the course of corticosteroids. In women with a complete course, 143 (41%) delivered within 7 days. The median interval between the course and delivery was 11 days and varied between 41 days in women with vaginal blood loss, 25 days in women with spontaneous preterm labor with intact membranes, and 8 days in women with preeclampsia (p<0.001). In women with spontaneous preterm labor with intact membranes and in women with vaginal blood loss, we can benefit substantially from a more accurate discrimination of women who need corticosteroids immediately and women who do not. [ABSTRACT FROM AUTHOR]

We sought to determine the rate of corticosteroid administration in preterm births in our institution and to describe factors associated with lack of corticosteroid exposure. We performed a retrospective case-control analysis. Of the 312 eligible women who delivered between 24 and 34 weeks' gestation, maternal corticosteroid administration was documented in 262 (84%) and no exposure in 50 (16%). A shorter admission to delivery interval (<48 hours) decreased the likelihood of corticosteroid administration (odds ratio [OR] 0.11, 95% confidence interval [CI] 0.03 to 0.28, p <0.001). Use of tocolytics was associated with a lower risk of corticosteroid nonexposure (OR 0.21, 95% CI 0.04 to 0.69, p=0.006). Lack of prenatal care was associated with an increased risk of corticosteroid nonexposure (OR 3.18, 95% CI 1.01 to 9.15, p=0.01). The likelihood of corticosteroid administration was also decreased by gestational ages at the upper limit of the spectrum (33 to 34 weeks; OR 0.22, 95% CI 0.09 to 0.53, p <0.001). The latter effect persisted after exclusion of premature rupture of membranes cases. In our population, factors associated with no maternal corticosteroid administration were shorter interval between admission and delivery, gestational age at the upper limit of the currently recommended interval for corticosteroid administration, and lack of prenatal care. [ABSTRACT FROM AUTHOR]